Project Summary Ex vivo genetic m odif ication of blood cells has proven transf orm ational in the treatm ent of hem atologic disorders, most notably the hematologic malignancies using CAR-T or TCR-T cells. Despite considerable investment and some clinical success, gene-modified T cell therapy manufacturing remains costly and inefficient. New delivery technologies are needed to serve this growing market and facilitate access to T cell therapies. The mission of CellFE is to simplify manufacturing of life-saving ex vivo gene therapies using our unique, rapid and efficient capability to deliver gene modifying cargo to patient?s cells. The goal of this project is to test, optimize and scale up a proprietary technology that relies on microfluidic transfection by mechanical manipulation (?mechanotransfection?) to engineer T cells to express transgenes, and simultaneously knock out immune receptors such as T cell receptor (TCR). While the focus of this project is strictly on gene modification of T cells, our platform technology has the potential to impact all ex vivo gene therapy applications, including other blood cells amenable to CAR technology.